1,10-Phenanthroline Potentiates Cytotoxicity of Hydroxyurea in Human Chronic Myeloid Leukemia Cells

Kamath, Narayana; Satyamoorthy, Kapaettu; Chitnis, M.P.; Advani, Suresh H.

doi:10.1159/000226713

Cited by 13 publications

(3 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may explain why concentrations of DEF in the millimolar order are needed to effectively prevent ROM damage in the preincubation protocol. In contrast, PHE is expected to easily permeate into cells because of its lipophilicity (the partition coefficient of PHE is approximately 3.5) (Kamath et al, 1989). Indeed, it has been shown that PHE can chelate Fez+ in the plasma membrane of erythrocytes within 2 min after addition (Nunez et al, 1983).…”

Section: Effects Of Def and Phe On Antioxidant Defensesmentioning

confidence: 99%

Reactive oxygen metabolite‐induced toxicity to cultured bovine endothelial cells: Status of cellular iron in mediating injury

Hiraishi

Terano

Razandi

et al. 1994

Journal Cellular Physiology

View full text Add to dashboard Cite

We aimed to determine the status of iron in mediating oxidant-induced damage to cultured bovine aortic endothelial cells. Chromium-51-labeled cells were exposed to reaction mixtures of xanthine oxidase/hypoxanthine and glucose oxidase/glucose; these produce superoxide and hydrogen peroxide, or hydrogen peroxide, respectively. Xanthine oxidase caused a dose dependent increase of 51Cr release. Damage was prevented by allopurinol, oxypurinol, and extracellular catalase, but not by superoxide dismutase. Prevention of xanthine oxidase-induced damage by catalase was blocked by an inhibitor of catalase, aminotriazole. Glucose oxidase also caused a dose-dependent increase of 51Ci release. Glucose oxidase-induced injury, which was catalase-inhibitable, was not prevented by extracellular superoxide dismutase. Both addition of and pretreatment with deferoxamine (a chelator of Fe3+) prevented glucose oxidase-induced injury. The presence of phenanthroline (a chelator of divalent Fe2+) prevented glucose oxidase-induced 51Cr release, whereas pretreatment with the agent did not. Apotransferrin (a membrane impermeable iron binding protein) failed to influence damage. Neither deferoxamine nor phenanthroline influenced cellular antioxidant defenses, or inhibited lysis by non-oxidant toxic agents. Treatment with allopurinol and oxypurinol, which inhibited cellular xanthine oxidase, failed to prevent glucose oxidase injury. We conclude that (1) among the oxygen species extracellularly generated by xanthine oxidase/hypoxanthine, hydrogen peroxide induces damage via a reaction on cellular iron; (2) deferoxamine and phenanthroline protect cells by chelating Fe3+ and Fe2+, respectively; and (3) reduction of cellular stored iron (Fe3+) to Fe2+ may be prerequisite for mediation of oxidant-induced injury, but this occurs independently of extracellular superoxide or cellular xanthine oxidase-derived superoxide.

show abstract

Section: Effects Of Def and Phe On Antioxidant Defensesmentioning

confidence: 99%

Reactive oxygen metabolite‐induced toxicity to cultured bovine endothelial cells: Status of cellular iron in mediating injury

Hiraishi

Terano

Razandi

et al. 1994

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…It reversibly inhibits two human prostate carcinoma cell lines: PC-3 and DU 145 [52], as well as formation of lymphoblastic Т-and В-cell colonies [53]. Being a bidentate chelating ligand for metal ions, 1,10-phenanthroline, when combined with the antitumor agent hydroxyurea, enhances the cytotoxicity of the latter with respect to human chronic myeloid leukemia cell line [54].…”

Section: Introductionmentioning

confidence: 99%

Reaction with DNA and pharmacologic activity of 1,10-phenanthroline and electron-rich 1,10-phenanthrocyanine complexes of d-elements

et al. 2012

View full text Add to dashboard Cite

“…Both ADR and MITO intercalate into double stranded DNA and induce formation of DNA strand breaks (6,7). Further in vivo and in vitro cross resistance pattern of MITO has been shown in human and murine tumors displaying the pleiotropic or multidrug resistant (MDR) phenomenon (8)(9)(10), which is characterized by a simultaneous expression of resistance to a variety of functionally and structurally unrelated compounds (11,12). The MDR phenotype is associated with elevated levels of a high molecular weight glycoprotein (13)(14)(15), (termed as P-glycoprotein), which functions as ATP-dependent efflux pump (16)(17)(18), facilitating the transport of anticancer drugs from the intracellular to the extracellular environment (19)(20).…”

mentioning

confidence: 99%

Evaluation of Quinidine Effect on the Antitumor Activity of Adriamycin and Mitoxantrone in Adriamycin-Sensitive and -Resistant P388 Leukemia Cells

Parekh¹,

Chitnis²

1990

Selective Cancer Therapeutics

View full text Add to dashboard Cite

Utilizing the P388 murine leukemia cells sensitive (P388/S) and resistant (P388/ADR) to Adriamycin (ADR), we evaluated the effect of quinidine, an anti-arrhythmic agent, on the cytotoxic activity of ADR and Mitoxantrone (MITO), both in vitro as well as in vivo. Quinidine enhanced the cytotoxicity of both ADR and MITO in P388/S and P388/ADR cells, as assessed by the decrease in color intensity of formazan crystal in the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. A dose dependent inhibition of 3H-thymidine and 3H-uridine incorporation was observed when the P388/S and P388/ADR cells were exposed to quinidine alone. A non-toxic concentration of quinidine (5 microM) enhanced the DNA biosynthesis inhibition induced by ADR (55 to 65%) and MITO (37 to 44%) in P388/ADR cells, indicating reversal of resistance, while in P388/S cells only a minimal increase in DNA biosynthesis inhibition was observed. The combination of quinidine at doses of 50 to 100 mg/kg significantly potentiated the antitumor activity of ADR and MITO in P388/ADR bearing mice, whereas the potentiation of ADR and MITO antitumor response was lower in P388/S bearing mice. Quinidine increased the cellular levels of ADR by 53 to 126% in P388/ADR cells in vitro, but failed to indicate such elevated levels of cellular ADR in P388/S cells. This enhanced intracellular accumulation of ADR in P388/ADR cells, explains the therapeutic efficacy of ADR and MITO in P388/ADR, both in vitro as well as in vivo. Results suggest the efficacy of quinidine to ameliorate the antitumor effects of ADR and MITO in drug resistant tumor cells.

show abstract

1,10-Phenanthroline Potentiates Cytotoxicity of Hydroxyurea in Human Chronic Myeloid Leukemia Cells

Cited by 13 publications

References 13 publications

Reactive oxygen metabolite‐induced toxicity to cultured bovine endothelial cells: Status of cellular iron in mediating injury

Reactive oxygen metabolite‐induced toxicity to cultured bovine endothelial cells: Status of cellular iron in mediating injury

Reaction with DNA and pharmacologic activity of 1,10-phenanthroline and electron-rich 1,10-phenanthrocyanine complexes of d-elements

Evaluation of Quinidine Effect on the Antitumor Activity of Adriamycin and Mitoxantrone in Adriamycin-Sensitive and -Resistant P388 Leukemia Cells

Contact Info

Product

Resources

About